Phospholipase activity effect

Effects mediated through stimulation of phospholipase activity and mobilization of intracellular Ca +... 

Most of these effects of vitamin E deficiency can be attributed to membrane damage. In deficiency, there is an accumulation of lysophosphatidylcholine in membranes, which is cytolytic. The accumulation of lysophosphatidylcholine is a result of increased activity of phospholipase A. It is not clear whether a-tocopherol inhibits phospholipase A whether there is increased phospholipase activity because of increased peroxidation of polyunsaturated fatty acids in phospholipids, and hence an attempt at membrane Upid repair or whether the physicochemical effects of a-tocopherol on membrane organization and fluidity prevent the cytolytic actions of lysophosphatidylcholine (Douglas et al., 1986 Erin et al., 1986). 

Timegadine, a guanidine derivative, inhibits cyclo-oxygenase, lipoxygenase, and phospholipase activity. Reported adverse effects are skin rashes, oral lesions, epigastric pain, nausea, dysuria, dizziness, vertigo, and sleep disturbances. Liver enzyme changes and pneumonitis have also been described (1-4). 

Generation of lipid mediators. Ca -dependent phospholipase activation has been shown to stimulate synthesis of lipid mediators derived from arachidonic acid. The production of these lipid mediators can provoke both short- and long-range effects on bystander cells (e.g. (Bhakdi eta/., 1994 Suttorp efal., 1985 Suttorp eta/., 1992). 

Toxins pre-synaptic neurotoxins, polypeptides, all chemically related to phospholipase A but no link between the phospholipase activity and toxicity. Effects similar to a-glycerotoxin and latrotoxin qv, e.g. crotoxin, notexin, taipoxin and (3-bungarotoxin. 

Figure 4. Effect of pH on total phospholipase activity in A. culture filtrates of fungus grown on rye steep media + 10 mg PC for 7 days. B. Culture wash of fungus grown on lima bean agar for 14 days. C. Potato leaf, uninfected or infected for 7 days. D. Infected potato leaf (7 days) assayed in the presence of 5 mM dithioreitol (DTT-insensitive activity). DDT-sensitive activity was calculated by subtracting the phospholipase activity in the presence of DDT from that measured in the absence of DDT. Reproduced with permission from Ref. 4. Copyright 1984, Academic Press.

Jung KY, Endou H (1990) Mercury chloride as a possible phospholipase C activator effect on angiotensin Il-induced [Ca ]i transient in the rat early proximal tubule. Biochem Biophys Res Commun 173 606-613... 

Time-course studies were conducted in order to study the effects of various treatments on the levels of phospholipase activity in 100,000 g supernatant fractions from potato leaves (Fig. 1). The phospholipase activity in the 100,000 g supernatant remained constant for 60 minutes at 25 C (data not shown). In other control experiments the addition of 3 mM MgCl and 0.3 mM ATP to the 100,000 g supernatant fraction had no... 

Eicosapentaenoic add (Table 6) is easily incorporated into the cell membrane-bound phospholipids. It is a poor substrate for the cyclooxygenase/hydroper-oxidase enzymatic system, and only very small amounts of endproducts with three double bonds will be formed when compared with the relative effectiveness of arachidonate metabolism. In contrast, dcosapentaenoic add is a preferred substrate for product generation by the S-lipoxygenase in subcellular fractions of human and animal neutrophils [66,87], whereas docosahexaenoic add is also a markedly inferior substrate for leukotriene synthesis. Eicosapentaenoic acid appears to inhibit phospholipase activity, resulting in a decrease of aradiidonic acid release ([67] Fig. 4). Moreover, simultaneously with thromboxane A3 and prostaglandin I3 generation from eicosapentaenoic add, the synthesis of thromboxane A2 and prostacyclin (PGIj) from aradiidonic acid [47] decreases, mainly due to inhibitory effects on PGH synthase activity (Fig. 4). 

Activation of Mi, M3, and M5 mAChRs does not only lead to the generation of IP3 followed by the mobilization of intracellular Ca2+, but also results in the stimulation of phospholipase A2, phospholipase D, and various tyrosine kinases. Similarly, M2 and M4 receptor activation does not only mediate the inhibition of adenylyl cyclase, but also induces other biochemical responses including augmentation of phospholipase A2 activity. Moreover, the stimulation of different mAChR subtypes is also linked to the activation of different classes of mitogen-activated protein kinases (MAP kinases), resulting in specific effects on gene expression and cell growth or differentiation. 

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